Alkyne-aryl phosphodiesterase-4 inhibitors

A compound represented by Formula (I):

• 61
• or a pharmaceutically acceptable salt thereof, wherein
• R is H, —C1-6alkyl or —C3-6cycloalkyl;
• R1 is H, or a —C1-6alkyl, —C3-6cycloalkyl, —C1-6alkoxy, —C2-6alkenyl, —C3-6alkynyl, —C(O)—C1-6alkyl, —C(O)-aryl, —(C0-6alkyl)-SOn—(C1-6alkyl), —(C0-6alkyl)-SOn-(aryl), phenyl, heteroaryl, or heterocycloC3-7alkyl group, wherein any of the groups is optionally substituted with 1-3 independent —C1-6alkyl, —C1-6alkoxy, OH, —N(C0-6alkyl)(C0-6alkyl), —(C0-6alkyl)-SOn—(C1-6alkyl), nitro, CN, ═N—O—C1-6alkyl, —O—N═C1-6alkyl, or halogen substituents;
• R2 is absent, H, halogen, —C1-6alkyl, —C3-6cycloalkyl, —C1-6alkyl(C3-6cycloalkyl)(C3-6cycloalkyl), —C1-6alkoxy, phenyl, heteroaryl, heterocycloC3-7alkyl, nitro, CN, ═N—O—C1-6alkyl, —O—N═C1-6alkyl, —N(C0-6alkyl)(C0-6alkyl), —NHSOn—(C1-6alkyl), —NHC(O)—C1-6alkyl, —NHC(O)-aryl, —C(O)—C1-6alkyl, —C(O)—O—C1-6alkyl, —C1-6alkyl(═N—OH), —C(N═NOH)C1-6alkyl, —C0-6alkyl(oxy)C1-6alkyl-phenyl, —SOnNH(C0-6alkyl), or —(C0-6alkyl)-SOn—(C1-6alkyl), wherein the phenyl, heteroaryl or heterocycloC3-7alkyl is optionally substituted with halogen, —C1-6alkyl, —C1-6alkoxy, hydroxy, —N(C0-6alkyl)(C0-6alkyl), or —C(O)—O—C1-6alkyl, and any alkyl is optionally substituted with 1-6 independent halogen or —OH substituents;
• n is 0, 1, or 2;
• R3 is absent, H, OH, —N(C0-6alkyl)(C0-6alkyl), halogen or C1-6alkyl, wherein any alkyl is optionally substituted with 1-6 independent halogen, OH, or —N(C0-6alkyl)(C0-6alkyl) substituents;
• R4, R5, R6, and R7 each independently is H, halogen, —C1-6alkyl, —C1-6alkoxy, —SOn—(C1-6alkyl), nitro, CN, or —N(C0-6alkyl)(C0-6alkyl), and any alkyl is optionally substituted with 1-6 independent halogen or —OH substituents;
• and
• R8 is phenyl, pyridyl, pyrimidyl, indolyl, quinolinyl, thienyl, pyridonyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, or imidazolyl;
• or oxides thereof when R8 is a heteroaryl;
• or H, —C1-6alkyl, or —C3-6cycloalkyl, and any alkyl is optionally substituted with 1-6 independent halogen, —N(C0-6alkyl)(C0-6alkyl), —N(C3-7cycloalkyl)(C0-6alkyl), —N(C3-7cycloalkyl)(C3-7cycloalkyl), N-heterocycloC4-7alkyl, —SOn—(C1-6alkyl), —SOn-(aryl), or —OH substituents.